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Najafov, A., Shpiro, N. & Alessi, D.R.Akt is efficiently activated by PIF-pocket- and PtdIns(3,4,5)P3-dependent mechanisms leading to resistance to PDK1 inhibitors. Biochem. J.448, 285–295 (2012).Together with ref. 42, this article provides evidence of an alternative mechanism for Akt activation by PDK1 that is independent of PDK1-PtdIns(3,4,5)P3 binding. This work shows how mTORC2-mediated phosphorylation of Ser473 in Aktrecruits PDK1 via a substrate-docking motif termed the PIF-pocket, allowing phosphorylation of Akt Thr308 by PDK1 and efficient Akt activation.

Delgoffe, G.M.et al.The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol.12, 295–303 (2011).This article provides key evidence about the specific role of mTORC1 and mTORC2 complexes in T cell function. In Rheb-deficient mice with disabled mTORC1 function, TH1 and TH17 responses are impaired both in vitro and in vivo; in RICTOR-deficient mice in which mTORC2 function is ablated, T cells fail to generate TH2 responses.

Shi, L.Z.et al.HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med.208, 1367–1376 (2011).This work shows that TH17 differentiation requires the upregulation of glycolytic activity and that the mTORC1-regulated expression of the transcription factor HIF1α is a crucial mediator of glycolytic pathways. Together with ref. 81 this article defines key role for mTORC1-HIF1α axis in the maintenance of glucose metabolism and glycolysis in effector T cells.